ArticleNeurotoxicity research2009
Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline reverses the neurotoxic effects of the prion protein fragment 90-231.
Article in Neurotoxicity research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Mechanism analysis and intervention strategies of the inflammatory microenvironment in traumatic spinal cord injury.Frontiers in immunology · 2025Review
- The expression of pro-prion, a transmembrane isoform of the prion protein, leads to the constitutive activation of the canonical Wnt/β-catenin pathway to sustain the stem-like phenotype of human glioblastoma cells.Cancer cell international · 2024Article
- Proteostasis unbalance in prion diseases: Mechanisms of neurodegeneration and therapeutic targets.Frontiers in neuroscience · 2022Review
- Neuroprotective effects of minocycline on focal cerebral ischemia injury: a systematic review.Neural regeneration research · 2020Review
- Emerging Role of Cellular Prion Protein in the Maintenance and Expansion of Glioma Stem Cells.Cells · 2019Review
- Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death.Cell death & disease · 2018Article
- Different Molecular Mechanisms Mediate Direct or Glia-Dependent Prion Protein Fragment 90-231 Neurotoxic Effects in Cerebellar Granule Neurons.Neurotoxicity research · 2017Article
- Minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury.Neural regeneration research · 2017Review
- Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells.Oncotarget · 2016Article
- Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells.Molecular neurobiology · 2016Article
- Analyses of the similarity and difference of global gene expression profiles in cortex regions of three neurodegenerative diseases: sporadic Creutzfeldt-Jakob disease (sCJD), fatal familial insomnia (FFI), and Alzheimer's disease (AD).Molecular neurobiology · 2014Article
- Comparative analysis of gene expression profiles between cortex and thalamus in Chinese fatal familial insomnia patients.Molecular neurobiology · 2013Article
- Excitotoxicity through NMDA receptors mediates cerebellar granule neuron apoptosis induced by prion protein 90-231 fragment.Neurotoxicity research · 2013Article
- Calcium binding promotes prion protein fragment 90-231 conformational change toward a membrane destabilizing and cytotoxic structure.PloS one · 2012Article
- Role of prion protein aggregation in neurotoxicity.International journal of molecular sciences · 2012Review
- Efficacy of novel acridine derivatives in the inhibition of hPrP90-231 prion protein fragment toxicity.Neurotoxicity research · 2011Article
- Human PrP90-231-induced cell death is associated with intracellular accumulation of insoluble and protease-resistant macroaggregates and lysosomal dysfunction.Cell death & disease · 2011Article
- Evidence for neuroinflammatory and microglial changes in the cerebral response to sleep loss.Sleep · 2011Article
- Reductions in amyloid-beta-derived neuroinflammation, with minocycline, restore cognition but do not significantly affect tau hyperphosphorylation.Journal of Alzheimer's disease : JAD · 2010Article
- Heterogeneity of microglia and TNF signaling as determinants for neuronal death or survival.Neurotoxicology · 2009Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several in vitro and in vivo studies addressed the identification of molecular determinants of the neuronal death induced by PrP(Sc) or related peptides. We developed an experimental model to assess PrP(Sc) neurotoxicity using a recombinant polypeptide encompassing amino acids 90-231 of human PrP (hPrP90-231) that corresponds to the protease-resistant core of PrP(Sc) identified in prion-infected brains. By means of mild thermal denaturation, we can convert hPrP90-231 from a PrP(C)-like conformation into a PrP(Sc)-like structure. In virtue of these structural changes, hPrP90-231 powerfully affected the survival of SH-SY5Y cells, inducing caspase 3 and p38-dependent apoptosis, while in the native alpha-helix-rich conformation, hPrP90-231 did not induce cell toxicity. The aim of this study was to identify drugs able to block hPrP90-231 neurotoxic effects, focusing on minocycline, a tetracycline with known neuroprotective activity. hPrP90-231 caused a caspase 3-dependent apoptosis via the blockade of ERK1/2 activation and the subsequent activation of p38 MAP kinase. We propose that hPrP90-231-induced apoptosis is dependent on the inhibition of ERK1/2 responsiveness to neurotrophic factors, removing a tonic inhibition of p38 activity and resulting in caspase 3 activation. Minocycline prevented hPrP90-231-induced toxicity interfering with this mechanism: the pretreatment with this tetracycline restored ERK1/2 activity and reverted p38 and caspase 3 activities. The effects of minocycline were not mediated by the prevention of hPrP90-231 structural changes or cell internalization (differently from Congo Red). In conclusion, minocycline elicits anti-apoptotic effects against the neurotoxic activity of hPrP90-231 and these effects are mediated by opposite modulation of ERK1/2 and p38 MAP kinase activities.
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